REAGENT COMPOSITION FOR DETECTING ILLICIT DRUGS AND SHEET KIT FOR DETECTING ILLICIT DRUGS COMPRISING SAME

Abstract

The present disclosure provides a reagent composition for detecting illicit drugs, the composition comprising: a diacetylene derivative compound represented by chemical formula 1; and at least one compound selected from among gabazine (SR-95531), an amine group-linked diacetylene derivative represented by chemical formula 2-1, and a gabazine-linked diacetylene derivative represented by chemical formula 2-2.

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Claims

1. A reagent composition for detecting illicit drugs, comprising: a diacetylene derivative compound represented by the following Chemical Formula 1; and at least one compound selected from the group consisting of gabazine, an amine group-linked diacetylene derivative represented by the following Chemical Formula 2-1, and a gabazine-linked diacetylene derivative represented by the following Chemical Formula 2-2, and optionally, further comprising a polyethylene glycol-based compound; and a thermoplastic fluorine polymer compound: ##STR00022## ##STR00023## ##STR00024## in Chemical Formula 1, Chemical Formula 2-1 or Chemical Formula 2-2, R.sub.1 is a C.sub.1-C.sub.15 alkyl group, R.sub.2 is a C.sub.1-C.sub.10 alkylene group, and R.sub.3 is -NH-C.sub.1-C.sub.6 alkylene group or a C.sub.1-C.sub.6 alkylene group.

2. The reagent composition of claim 1, wherein the reagent composition comprises: the diacetylene derivative compound represented by Chemical Formula 1; gabazine; the polyethylene glycol-based compound; and the thermoplastic fluorine polymer compound.

3. The reagent composition of claim 1, wherein the reagent composition comprises: the diacetylene derivative compound represented by Chemical Formula 1; the amine group-linked diacetylene derivative represented by Chemical Formula 2-1; the polyethylene glycol-based compound; and the thermoplastic fluorine polymer compound.

4. The reagent composition of claim 1, wherein the reagent composition comprises: the diacetylene derivative compound represented by Chemical Formula 1; the gabazine-linked diacetylene derivative represented by the following Chemical Formula 2-2; the polyethylene glycol-based compound; and the thermoplastic fluorine polymer compound.

5. The reagent composition of claim 1, wherein the reagent composition further comprises a polyester-based compound or gelatin, and the polyester-based compound is at least one selected from the group consisting of polycaprolactone (PCL), polyglycolide, poly(lactic acid), polyhydroxyalkanoate (PHA), polyhydroxybutyrate, poly(lactic-co-glycolic acid), polybutylene succinate (PBS), and polyethylene terephthalate.

6. The reagent composition of claim 1, wherein the diacetylene derivative compound represented by Chemical Formula 1 is a compound represented by the following Chemical Formula 3, the amine group-linked diacetylene derivative represented by Chemical Formula 2-1 is a compound represented by the following Chemical Formula 4, and the gabazine-linked diacetylene derivative represented by the following Chemical Formula 2-2 is a compound represented by the following Chemical Formula 6: ##STR00025## ##STR00026## ##STR00027## .

7. The reagent composition of claim 1, wherein the reagent composition comprises, based on the total weight of the composition, 0.05 to 0.5 wt% of the diacetylene derivative compound represented by Chemical Formula 1; 0.05 to 0.5 wt% of gabazine; 0.5 to 5 wt% of the polyethylene glycol-based compound; and 5 to 20 wt% of the thermoplastic fluorine polymer compound.

8. The reagent composition of claim 1, wherein the reagent composition comprises, based on the total weight of the composition, 0.05 to 0.5 wt% of the diacetylene derivative compound represented by Chemical Formula 1; 0.01 to 0.2 wt% of the amine group-linked diacetylene derivative represented by Chemical Formula 2-1; 1 to 15 wt% of the polyethylene glycol-based compound; and 1 to 15 wt% of the thermoplastic fluorine polymer compound.

9. The reagent composition of claim 1, wherein the reagent composition comprises, based on the total weight of the composition, 0.05 to 0.5 wt% of the diacetylene derivative compound represented by Chemical Formula 1; 0.05 to 0.5 wt% of the gabazine-linked diacetylene derivative compound represented by Chemical Formula 2-2; 0.5 to 10 wt% of the polyethylene glycol-based compound; and 5 to 20 wt% of the thermoplastic fluorine polymer compound.

10. The reagent composition of claim 1, wherein the polyethylene glycol-based compound is at least one selected from the group consisting of poly(ethylene oxide) (PEO), polyethylene glycol, and polyoxyethylene, and the thermoplastic fluorine polymer compound is at least one selected from the group consisting of polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), polyvinylidene fluoride, and polychlorotrifluoroethylene.

11. The reagent composition of claim 1, wherein the illicit drug is selected from the group consisting of gamma-hydroxybutyric acid (GHB), ketamine, rohypnol, philopon, ecstasy, zolpidem, cocaine, and heroin.

12. A method for producing a sheet kit for detecting illicit drugs, comprising: (S1) preparing a spinning solution containing a reagent composition; (S2) forming a sheet by electrospinning the spinning solution; and (S3) UV-treating the sheet, wherein the reagent composition comprises a diacetylene derivative compound represented by the following Chemical Formula 1; and at least one compound selected from the group consisting of gabazine, an amine group-linked diacetylene derivative represented by the following Chemical Formula 2-1, and a gabazine-linked diacetylene derivative represented by the following Chemical Formula 2-2, and optionally, further comprising a polyethylene glycol-based compound; and a thermoplastic fluorine polymer compound: ##STR00028## ##STR00029## ##STR00030## in Chemical Formula 1, Chemical Formula 2-1 or Chemical Formula 2-2, R.sub.1 is a C.sub.1-C.sub.15 alkyl group, R.sub.2 is a C.sub.1-C.sub.10 alkylene group, and R.sub.3 is -NH-C.sub.1-C.sub.6 alkylene group or a C.sub.1-C.sub.6 alkylene group.

13. The method of claim 12, wherein in step (S2), the electrospinning is performed under the conditions that a distance between an electrode and a collector is 16 to 20 cm; an applied voltage is 15 to 25 kV; a temperature is 25 to 35° C.; and a discharge rate of the spinning solution is 1 to 6 mL/hr.

14. (canceled)

15. A method for detecting illicit drugs, comprising: contacting a detection sample with a sheet kit containing a reagent composition, wherein the reagent composition comprises a diacetylene derivative compound represented by the following Chemical Formula 1; and at least one compound selected from the group consisting of gabazine, an amine group-linked diacetylene derivative represented by the following Chemical Formula 2-1, and a gabazine-linked diacetylene derivative represented by the following Chemical Formula 2-2, and optionally, further comprising a polyethylene glycol-based compound; and a thermoplastic fluorine polymer compound: ##STR00031## ##STR00032## ##STR00033## in Chemical Formula 1, Chemical Formula 2-1 or Chemical Formula 2-2, R.sub.1 is a C.sub.1-C.sub.15 alkyl group, R.sub.2 is a C.sub.1-C.sub.10 alkylene group, and R.sub.3 is -NH-C.sub.1-C.sub.6 alkylene group or a C.sub.1-C.sub.6 alkylene group, and wherein the sheet kit is obtained by electrospinning of the reagent composition.

16. The method of claim 15, wherein a color change is observed in the sheet kit for detecting illicit drugs when the detection sample contains illicit drugs.

17. The method of claim 15, wherein the illicit drug is selected from the group consisting of gamma-hydroxybutyric acid (GHB), ketamine, rohypnol, philopon, ecstasy, zolpidem, cocaine, and heroin.

18. The method of claim 15, wherein the reagent composition comprises: the diacetylene derivative compound represented by Chemical Formula 1; gabazine; the polyethylene glycol-based compound; and the thermoplastic fluorine polymer compound.

19. The method of claim 15, wherein the reagent composition comprises: the diacetylene derivative compound represented by Chemical Formula 1; the amine group-linked diacetylene derivative represented by Chemical Formula 2-1; the polyethylene glycol-based compound; and the thermoplastic fluorine polymer compound.

20. The method of claim 15, wherein the reagent composition further comprises a polyester-based compound or gelatin, and the polyester-based compound is at least one selected from the group consisting of polycaprolactone (PCL), polyglycolide, poly(lactic acid), polyhydroxyalkanoate (PHA), polyhydroxybutyrate, poly(lactic-co-glycolic acid), polybutylene succinate (PBS), and polyethylene terephthalate.

21. The method of claim 15, wherein the diacetylene derivative compound represented by Chemical Formula 1 is a compound represented by the following Chemical Formula 3, the amine group-linked diacetylene derivative represented by Chemical Formula 2-1 is a compound represented by the following Chemical Formula 4, and the gabazine-linked diacetylene derivative represented by the following Chemical Formula 2-2 is a compound represented by the following Chemical Formula 6: ##STR00034## ##STR00035## ##STR00036## .

Description

DESCRIPTION OF DRAWINGS

[0072] FIG. 1 shows an NMR analysis result of gabazine prepared according to Example 1 of the present disclosure.

[0073] FIG. 2 shows a FT-IR analysis result of PCDA-NH.sub.2 prepared according to Example 2-1 of the present disclosure.

[0074] FIG. 3 shows an NMR analysis result of PCDA-NH.sub.2 prepared according to Example 2-1 of the present disclosure.

[0075] FIG. 4 is a schematic diagram showing a production process of a sheet kit containing a reagent composition according to the present disclosure.

[0076] FIG. 5 shows a detection result of GHB in the sheet kit containing the reagent composition of Example 4-1 according to the present disclosure.

[0077] FIG. 6 shows an NMR analysis result of PCDA-gabazine prepared according to Example 2-2 of the present disclosure.

[0078] FIG. 7 is a schematic diagram showing a sheet kit for sensing GHB containing the reagent composition of the present disclosure.

[0079] FIG. 8 shows a process for producing a sheet kit containing the reagent composition of the present disclosure through electrospinning.

[0080] FIG. 9 shows GHB detection results of the sheet for drug detection of Examples 4-2 and 4-3 according to the present disclosure.

[0081] FIG. 10 shows the detection results of GHB dissolved in various beverages of the sheet for drug detection of Example 4-3 according to the present disclosure.

[0082] FIG. 11 shows a SEM image of the sheet for drug detection produced according to the present disclosure.

BEST MODE

[0083] Hereinafter, the present disclosure will be described in more detail through Examples. However, these Examples are provided to illustrate the present disclosure by way of example, and the scope of the present disclosure is not limited to these Examples.

Example 1: Synthesis of Gabazine

[0084] ##STR00021##

[0085] Gabazine was synthesized in the same order as shown in Reaction Scheme 1 above by a method described in the document “Org. Biomol. Chem., 2010, 8, 4131-4136”. The structure of the prepared gabazine was confirmed through NMR analysis, and results thereof are shown in FIG. 1.

Example 2: Preparation of Diacetylene Derivative Compound

Example 2-1: Synthesis of Amine Group-Linked Diacetylene Derivative Compound (PCDA-NH.SUB.2.)

(Step 1) Synthesis of PCDA-NHS

[0086]

[0087] A solution was prepared by dissolving 10,12-pentacosadiynoic acid (PCDA) (2.67 mmol, 1 g) and 1-ethyl-3-[3-dimethyl-aminopropyl]carbodiimide hydrochloride (EDC) (4 mmol, 620 mg) in 50 mL of dichloromethane (DCM). To the prepared solution, N-hydroxysuccinimide (NHS) (4 mmol, 460 mg) was added, and the mixture was stirred at room temperature for 8 hours. After the reaction, the organic solvent was removed by evaporation under a vacuum atmosphere, and then the crude product was poured into distilled water and extracted three times with ethyl acetate for purification. Then, the organic solvent was dried over anhydrous magnesium sulfate and concentrated in vacuum to obtain a white powder.

[0088] It was confirmed through thin layer chromatography (TLC, hexane/ethyl acetate, 3:1) and 1H-NMR (600 MHz, DMSO-d6) that the white powder obtained after concentration was PCDA-NHS. .sup.1H-NMR peak values of the prepared PCDA-NHS are as follows.

[0089] .sup.1H-NMR (600 MHz) 5(ppm) : 0.86 (t, 3H), 1.24-1.62 (m, 32H), 2.27 (t, 4H), 2.65 (t, 2H), 2.81 (s, 4H).

(Step 2) Synthesis of PCDA-NH.SUB.2

[0090] A solution containing 50 mL of dichloromethane and PCDA-NHS (1 mmol, 472 mg) prepared in step 1 was slowly added dropwise to 50 mL of dichloromethane solution containing ethylenediamine (EDA) (50 mmol, 3 g), and the mixture was stirred at room temperature overnight. After the reaction, the organic solvent was removed through filtration, and the resulting product was purified by extraction three times using water and dichloromethane. Subsequently, the organic solvent was removed using anhydrous magnesium sulfate and the resulting product was concentrated in vacuum to obtain PCDA-NH.sub.2 in the form of a light-blue powder.

[0091] It was confirmed through thin layer chromatography (TLC, methanol/ethyl acetate, 3:7), FT-IR, and 1H-NMR (600 MHz, DMSO-d6) that the obtained light-blue powder was PCDA-NH.sub.2. 1H-NMR analysis results of the prepared PCDA-NH.sub.2 are shown in FIG. 3, and the peak values are as follows. In addition, the FT-IR analysis results of PCDA-NH.sub.2 are shown in FIG. 2.

[0092] .sup.1H-NMR(600 MHz) δ (ppm) : 0.88 (t, 3H), 1.26-1.63 (m, 32H), 2.18 (t, 2H), 2.24 (t, 4H), 2.83 (m, 2H), 3.30 (q, 2H), 5.86 (brs, 1H)

Example 2-2: Synthesis of Gabazine-Linked Diacetylene Derivative Compound (PCDA-Gabazine)

[0093]

[0094] 442 mg (1.2 mmol) of Gabazine prepared according to Example 1 was dissolved in 20 mL of dimethylformamide (DMF). Then, 372 mg (2.4 mmol) of 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC), and 276 mg (2.4 mmol) of N-hydroxysuccinimide (NHS) were added, followed by stirring at room temperature for 8 hours to proceed with the reaction. Then, 419 mg (1 mmol) of PCDA-NH.sub.2 prepared according to Example 2-1 was added to the reaction mixture and stirred overnight at room temperature to prepare a mixture. Then, for purification, the mixture was extracted with ethyl acetate and DMF was removed with distilled water (3 times). Then, the organic solvent was dried over anhydrous magnesium sulfate and concentrated in vacuum to obtain a light-blue powder.

[0095] It was confirmed through thin layer chromatography (TLC, methanol/ethyl acetate, 3:7), and 1H-NMR spectroscopy (600 MHz, CDCl.sub.3) that the obtained light-blue powder was PCDA-gabazine.

[0096] .sup.1H-NMR analysis results of the prepared PCDA-gabazine are shown in FIG. 7, and specific peak values are as follows.

[0097] .sup.1H-NMR(600 MHz) 5(ppm) : 0.85 (t, 3H), 1.24-1.44 (m, 32H), 2.03 (t, 2H), 2.27 (t, 4H), 2.38 (t, 2H), 2.76 (m, 2H), 3.07 (m, 2H), 3.31 (d, 2H), 3.81 (s, 3H), 7.03-7.15 (m. 2H), 7.77-7.85 (m. 2H), 7.94-8.01 (m, 4H), 8.30 (m, 1H).

Example 3: Preparation of Reagent Composition For Detecting Illicit Drugs

Example 3-1: Preparation of Reagent Composition 1 (PCDA+PEO+PVDF+PCDA-NH.SUB.2.)

[0098] 450 mg of Polyvinylidene fluoride (PVDF) having a weight average molecular weight of 400,000 was dissolved in a mixed solvent containing 1.28 g of N-methyl-2-pyrrolidone (NMP) and 5.98 g of acetone, and 450 mg of poly(ethylene oxide) (PEO) having a weight average molecular weight of 2000 to 3000 was added thereto. After mixing thoroughly, 18 mg of 10,12-pentacosadiynoic acid (PCDA) and 4.5 mg of PCDA-NH.sub.2 prepared according to Example 2-1 were added and mixed to be dispersed well, thereby preparing Reagent Composition 1.

Example 3-2: Preparation of Reagent Composition 2 (PCDA+PEO+PVDF+Gabazine)

[0099] 810 mg of Polyvinylidene fluoride (PVDF) having a weight average molecular weight of 400,000 and 90 mg of poly(ethylene oxide) (PEO) having a weight average molecular weight of 2000 to 3000 were dissolved in 1.28 g of N-methyl-2-pyrrolidone (NMP) to prepare a matrix solution to be used as a matrix layer.

[0100] In addition, 11.25 mg of 10,12-pentacosadiynoic acid (PCDA) and 11.25 mg of gabazine prepared according to Example 1 were dissolved in a mixed solvent containing 4.5 g of acetone and 0.16 ml of methanol to prepare a sensing solution.

[0101] The prepared matrix solution and sensing solution were uniformly mixed at a temperature of 40° C., thereby preparing Reagent Composition 2.

Example 3-3: Preparation of Reagent Composition 3 (PCDA+PEO+PVDF+PCDA-Gabazine)

[0102] 600 mg of Polyvinylidene fluoride (PVDF) having a weight average molecular weight of 400,000 and 300 mg of poly(ethylene oxide) (PEO) having a weight average molecular weight of 2000 to 3000 were dissolved in 1.7 g of N-methyl-2-pyrrolidone (NMP) to prepare a matrix solution to be used as a matrix layer.

[0103] In addition, 18 mg of 10,12-pentacosadiynoic acid (PCDA) and 4.50 mg of PCDA-gabazine prepared according to Example 2-2 were dissolved in 4.9 g of acetone to prepare a sensing solution.

[0104] The prepared matrix solution and sensing solution were uniformly mixed at a temperature of 40° C., thereby preparing Reagent Composition 3.

Example 4: Production of Sheet for Detecting Illicit Drugs Using Electrospinning

Example 4-1: Production of Sheet for Drug Detection Comprising Reagent Composition 1

[0105] The reagent composition prepared according to Example 3-1 was subjected to electrospinning. When electrospinning the prepared solution, a sheet paper was produced by electrospinning for 2 hours under conditions that a distance between an electrode and a collector is 18.5 cm, an applied voltage is 20 kV, a temperature is 28° C., and a discharge rate of a spinning solution is 3 mL/hr. The produced sheet was processed into various sizes and irradiated with 254 nm UV for 10 seconds to produce a sheet for detecting illicit drugs.

Example 4-2: Production of Sheet for Drug Detection Comprising Reagent Composition 2

[0106] The reagent composition 2 prepared according to Example 3-2 was subjected to electrospinning. When electrospinning the prepared solution, a sheet paper was produced by electrospinning for 2 hours under conditions that a distance between an electrode and a collector is 18.5 cm, an applied voltage is 20 kV, a temperature is 28° C., and a discharge rate of a spinning solution is 3 mL/hr. The produced sheet was processed into various sizes and irradiated with 254 nm UV for 10 seconds to produce a sheet for detecting illicit drugs.

Example 4-3: Production of Sheet for Drug Detection Comprising Reagent Composition 3

[0107] The reagent composition 3 prepared according to Example 3-3 was subjected to electrospinning. When electrospinning the prepared solution, a sheet paper was produced by electrospinning for 2 hours under conditions that a distance between an electrode and a collector is 18.5 cm, an applied voltage is 20 kV, a temperature is 28° C., and a discharge rate of a spinning solution is 3 mL/hr. The produced sheet was processed into various sizes and irradiated with 254 nm UV for 10 seconds to produce a sheet for detecting illicit drugs.

Example 5: Drug Detection Using Sheet for Drug Detection of the Present Disclosure

Example 5-1: GHB Detection Characteristics According to GHB Content

[0108] The illicit drug GHB (legally obtained with permission from the Ministry of Food and Drug Safety (MFDS); Permission No. 443) was dissolved in water to prepare samples of 1 to 5% concentration, respectively, and water in which no illicit drugs were dissolved was used as a control group (0%).

[0109] Each of the prepared 1% to 5% sample and the control group (0%) was dropped on the sheets produced according to Example 4-2 and Example 4-3, and the color change depending on the drug concentration was observed. Results thereof are shown in FIG. 10.

[0110] Referring to FIG. 9, it could be confirmed that when the control group (0%) was in contact with the sheet containing the reagent composition according to the present disclosure, no color change occurred, whereas when the sample containing the GHB drug was in contact with the sheet, the color change from blue to red occurred even at the GHB concentration of 1%. In particular, as compared to the control group (water; 0%), the sheet containing the reagent composition 3 of the present disclosure (Example 4-3) showed a significant increase in red intensity when contacted with GHB regardless of the concentration of the GHB drug.

[0111] Therefore, the sheet for detecting illicit drugs according to the present disclosure may easily check the presence or absence of illicit drugs through color change.

Example 5-2: GHB Detection Characteristics According to the Type of Solvent in Which GHB is Dissolved

[0112] Since GHB has colorless, odorless, and tasteless characteristics, it is not easy to ascertain its existence, and especially when mixed with various non-alcoholic or alcoholic beverages, it is more difficult to confirm its existence. Therefore, the ability of the sheet of the present disclosure to detect GHB was evaluated using various beverages containing GHB as solvents.

[0113] Water, sports drinks, carbonated drinks, yogurt (Yakult) and coffee were used as non-alcoholic beverages, soju, beer, cognac, and wine were used as alcoholic beverages. Then, GHB, an illicit drug, was dissolved in the above-described beverages as solvents to prepare samples at a concentration of 4 to 5%, respectively, and a sample in which the illicit drug was not dissolved was used as a control group (without GHB or GHB free drink).

[0114] Color change according to the type of solvent in which the drug was dissolved was observed by dropping each of the prepared samples and control group on sheets produced according to Example 4-1 and Example 4-3. Results thereof are shown in FIGS. 5 and 10.

[0115] Referring to FIGS. 5 and 10, it could be confirmed that the color of the sheet changed from blue to red regardless of the type of solvent in which GHB was dissolved. In general, GHB is known to occur naturally in red wine by fermentation of red grapes (4.1 to 21.4 mg/L), and even in the absence of GHB, various additives in beverages may cause unintended color changes. However, the sheet containing the reagent composition of the present disclosure showed a clear color change when GHB was present even in a small amount, and thus the presence or absence of GHB could be easily confirmed with the naked eye without the use of sophisticated analysis equipment. Also, as time passed, the red color became more vivid and the intensity increased.

[0116] These results suggest that if the illicit drug GHB is present, the reagent composition of the present disclosure is able to easily detect the drug through color change regardless of the small amount of the drug or the type of solvent in which the illicit drug is dissolved.

[0117] From the above description, those skilled in the art to which the present disclosure pertains will understand that the present disclosure may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present disclosure should be construed as including all changes or modifications derived from the meaning and scope of the claims to be described below and equivalent concepts rather than the detailed description above are included in the scope of the present disclosure.